Analysis of EGFR gene mutations in lung adenocarcinoma in Karamay,Xinjiang,China

Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mutations in Karamay,Xinjiang,China.Methods:Paraffin-embedded tissue samples of adenocarcinoma patients were collected in the Karamay Central Hospital from March 2016 to June 2019,and mutations in exon 18–21 of the EGFR gene were detected by the allele-specific amplification polymerase chain reaction(Amplification RefractoryMutation System–PCR)method.The relationships between themutation types,mutation incidence,and clinical features were analyzed.Results:Of the 170 patients with lung adenocarcinoma,83 had EGFR mutations.The total mutation rate of EGFR in patients with lung adenocarcinoma was 48.8%,which included mutations in exons 18(1.2%[2/170]),19(19.4%[33/170]),20(2.4%[4/170]),and 21(20.6%[35/170]).Intriguingly,there was a case with 9 mutations in exons 20 and 21.The mutations in exon 19 of EGFR resulted in the deletion of codons 746 to 750.The main mutation in exon 21 was L858R(91.4%[32/35]).There was no significant difference in exons 19 and 21 mutation rates(P>0.05).The mutation rate of EGFR in female patients was significantly higher than that in male patients(P<0.05)but had no correlation with the age,smoking status,and clinical stage of patients with non–small cell lung cancer(P>0.05).The EGFR mutation rate may be related to the degree of tumor differentiation.Conclusions:Among patients with lung adenocarcinoma in Kelamayi(city in Xinjiang),EGFR mutations were more frequently detected in female patients,and the main sites of mutations were exons 19 and 21.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9

Objective:To explore whether the ethanol extract of Herpetospermum caudigerum Wall(EHC),a Xizang medicinal plant traditionally used for treating liver diseases,can improve imiquimod-induced psoriasis-like skin inflammation.Methods:Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice.The protein levels of interferon-γ(IFN-γ),tumor necrosis factor-a(TNF-a),and interleukin-17A(IL-17A)in mouse skin samples were examined using immunohistochemical staining.In vitro,IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1(ICAM-1)and chemokine CXC ligand 9(CXCL9)using Western blotting and reverse transcription-quantitative polymerase chain reaction.The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.Results:EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ,TNF-a,and IL-17A in psoriatic lesions.Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes.Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin–proteasome-mediated protein degradation rather than transcriptional repression.Seven primary compounds including ehletianol C,dehydrodiconiferyl alcohol,herpetrione,herpetin,herpetotriol,herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Conclusion:Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites.

Cardiovascular risk and prevalence of metabolic syndrome by differing criteria

Background The prevalence of metabolic syndrome （MetS） in hypertensive population in Chinese countryside is unknown. Firstly, this study compared the prevalence of MetS according to National Cholesterol Education Program （NCEP） ATPIII, revised NCEP and International Diabetes Federation （IDF） definitions. Secondly, it investigated the association between MetS, coronary heart disease （CHD） and stroke in patients with hypertension. Methods In this cross sectional study, the cluster sampling method was used. Three MetS definitions were applied to 1418 normal subjects and 5348 hypertensive patients aged 40-75 years in rural areas in China. The agreement between different MetS definitions was estimated by K statistics. Logistic regression analyses determined the association between MetS defined by the three MetS definitions and CHD and stroke. Results In subjects without hypertension, the prevalence of Mets was 4.1% by NCEP definition, 8.3% revised NCEP definition and 7.8% IDF definition. In hypertensive individuals, the prevalence was 14.0%, 32.9%, and 27.4% in men; 35.6%, 53.1%, and 50.2% in women by the same definitions, respectively. In hypertensive individuals, the agreement was 94.4% in men and 97.0% in women between revised NCEP and IDF definitions. The IDF defined MetS was more strongly associated with CHD than the NCEP or revised NCEP defined MetS （adjusted odds ratio： 1.92 compared with 1.85 and 1.69 in men; 1.64 compared with 1.48 and 1.60 in women）. Conclusions In the patients with hypertension, the revised NCEP and IDF definitions identified more individuals than NCEP definition and their agreement is very high. The IDF defined MetS is more strongly associated with CHD than the NCEP or revised NCEP defined MetS, but weakly or not associated with stroke.

Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population

Background The ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene （GHSR） is an excellent candidate for studying metabolic syndrome. This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population. Methods Subjects consisted of 698 patients aged 41 to 80 years, diagnosed as metabolic syndrome by International Diabetes Federation （IDF） 2005 criteria, and 762 age- and gender-matched controls. Three variants within the GHSR were selected and genotyped using polymerase chain reaction （PCR） and restriction fragment length polymorphism （RFLP）. Odds ratios were estimated using a case-control study design by controlling confounding factors. Results The NA genotype （rs2922126） in the promoter was associated with metabolic syndrome （OR 1.41, 95%C/ 1.03-1.94）, increased waist circumference （OR 1.75, 95%C/1.26-2.42）, and increased fast blood glucose （OR 1.49, 95%CI 1.07-2.06） in women. The NA genotype （rs509030） in the intron was associated with lower plasma high density lipoprotein in women （OR 1.37, 95%C/1.02-1.84）. Conclusion The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.